RISK FACTORS AT NON-UNION OF TIBIAL FRACTURE TREATED WITH INTRAMEDULLARY NAIL

ABSTRACT Objective: Identify the predictors associated with delayed union at 6 months and non-union at 12 months in tibial shaft fractures treated with intramedullary nailing (IMN). Methods: This retrospective longitudinal study included a cohort of 218 patients who sustained tibial shaft fractures and received IMN between January 2015 and March 2022. We gathered data on a range of risk factors, including patient demographics, trauma intensity, associated injuries, fracture characteristics, soft tissue injuries, comorbidities, addictions, and treatment-specific factors. We employed logistic bivariate regression analysis to explore the factors predictive of delayed union and non-union. Results: At the 6-month follow-up, the incidence of delayed union was 28.9%. Predictors for delayed union included flap coverage, high-energy trauma, open fractures, the use of external fixation as a staged treatment, the percentage of cortical contact in simple type fractures, RUST score, and postoperative infection. After 12 months, the non-union rate was 15.6%. Conclusion: the main predictors for non-union after IMN of tibial shaft fractures are related to the trauma energy. Furthermore, the initial treatment involving external fixation and postoperative infection also correlated with non-union. Level of Evidence III; Retrospective Longitudinal Study.


INTRODUCTION
Tibial shaft fractures are the most prevalent type of long bone fracture, demonstrating a bimodal distribution.Intramedullary nailing (IMN) stands as the primary treatment for displaced tibial shaft fractures 2 .Despite its effectiveness, complications such as delayed union and non-union continue to pose a substantial challenge, with reported incidence rates ranging from 4% to 48% 3,4 .
The consequences of delayed union and non-union extend beyond statistics.These complications impose additional burden on patients, necessitating revision surgeries and prolonging pain and disability.
Numerous previous studies have endeavored to shed light on the factors influencing non-union development, including patient demographics, injury and fracture characteristics, and aspects related to treatment 5,6 .However, the current body of literature remains marked by uncertainties and inconclusive findings regarding the precise risk factors for fracture healing disturbances 7,8 .The primary objectives of this study are to elucidate the risk factors and predictors associated with delayed union at 6 months and nonunion at 12 months following the intramedullary nailing treatment of tibial shaft fracture.  1.Healing: fracture was considered healed when patients had no pain in the fracture site, no limping and showed callus involving at least three of the four cortices and required additional surgical intervention beyond definitive fixation 13 .Lack of healing in 6 months was classified as delayed union and absence of healing at 12 months was classified as non-union.Follow up: assessment of screw breakage and deep infection.

This
Qualitative parameters assessed were described for all patients using absolute and relative frequencies and the qualitative characteristics were described using summary measures (mean and standard deviation).The occurrence of delayed union at 6 months and non-union at 12 months was described according to the qualitative characteristics using absolute and relative frequencies and the association was verified using chi-square tests or exact test (Fischer's exact test or likelihood ratio tests).The quantitative characteristics were described according to each outcome using summary measures and compared using Student's t-test.Unadjusted odds ratios (OR) were estimated with the respective 95% confidence intervals for each variable of interest for non-union in each period using bivariate logistic regression and joint models were created with the characteristics that had a descriptive level of less than 0.10 (p < 0.10) in the unadjusted analyzes, with the characteristics being present for all the patients in the study and whose numbers of patients in the categories were in agreement to be included in the analyzes, with the models being carried out using multiple logistic regression with full models, i.e., all the variables included in the models were kept in the final models 14,15 .
The IBM-SPSS for Windows version 22.0 software was used to carry out the analysis and Microsoft Excel 2013 was used to tabulate the data and create the graphs.The tests were carried out at a 5% significance level.

RESULTS
From January 2015 to March 2022, our cohort encompassed a total of 218 patients.The cohort exhibited a mean age of 36.2 ± 14.2 years, with a male predominance comprising 180 patients (82.6%).High-energy trauma constituted the etiological factor in 84.9% of the cases, and 50.5% of these cases presented with associated injuries, of which 52.7% were classified as AIS >3.(Table 1) The prevailing fracture type was the AO/OTA type A, accounting for 57.3% of the cases.The majority of the fractures were characterized as open injuries (63.3%), with 49.1% classified as Gustilo IIIA and 9.2% as Gustilo IIIB.Compartment syndrome occurred in only 5 (2.3%) cases.(Table 1) For a more comprehensive dataset of the patients' characteristics, please refer to Table 1.
The average interval between fracture occurrence and IMN fixation was 8.5 ± 5.7 days.Among the patients who underwent the staged treatment with the external fixator 135 (61.9), the average time to conversion into IMN was 6.  4) Multiple logistic regression analyses encompassing all risk factors revealed that, at the 6-month mark, patients who used an external fixator had a 5.99 times higher chance of experiencing delayed union compared to those who did not use one (p = 0.016).Furthermore, with each 1-point increase in RUST, the chance of delayed union decreased by 79% (p < 0.001), irrespective of other patient characteristics.Patients requiring flap reconstruction had a 2.99 times higher chance of non-union at 12 months compared to those without the need for a flap (p = 0.027).Patients subjected to prior external fixation had a 4-fold higher chance of non-union at 12 months compared to those who did not undergo external fixation (p = 0.031).Lastly, patients with postoperative deep infections had a 2.87 times higher chance of experiencing non-union, regardless of other patient characteristics.(Table 5)

DISCUSSION
Non-union, a distressing complication, may ensue after a fracture, imposing considerable physical and economic burdens.This phenomenon not only inflicts substantial pain, discomfort and functional impairment to the patient but also necessitates additional medical interventions, incurring in substantial expenses 13,16 .The importance of this issue is further exacerbated when it pertains to non-union arising from tibia shaft fractures, given their status as the most prevalent long bone fractures in adults 1,2 , thereby amplifying the magnitude of the problem.This is the first to study a population in Brazil and Latin America with a substantial sample size.Notably, the average age of our patient cohort stood at 36.2 ± 14.2, signifying a youthfulness in comparison to analogous studies such as Kawasaki N et al. 4 and Makaram NS et al. 17 , which reported mean ages of 45.6 and 46 years, respectively.This deviation may be explained to the unique characteristics of our institution -a tertiary trauma center entrusted with the most severe cases within the city's rescue system.Given the prominence of high-energy trauma, one might anticipate a concomitant prevalence of associated injuries.However, our study diverges from this expectation, revealing that nearly half of our patients (49.5%) presented without any associated injuries.Among those who did, the injuries tended to be minor in nature (AIS < 3).This phenomenon can be explained by the preponderance of motorcycle accidents within our city.Such incidents frequently result in extremity injuries while sparing the abdomen or thorax from trauma, thus accounting for this distribution of injury pattern.Among the 138 patients in our study, representing 63.3% of the total cohort, 107 patients (77.5%) presented with Gustilo IIIA lesions, while 20 patients (14.5%) exhibited type IIIB lesions, necessitating attention to soft tissue reconstruction with flap coverage.However, it is noteworthy that 29 patients underwent flap reconstruction, that is explained by the fact that nine patients from the Gustilo IIIA group encountered postoperative soft tissue complications, requiring debridement and subsequent soft tissue reconstruction.Both open fracture and need for flap had association with the incidence of delayed union at 6 months of 28.9% and non-union at 12 months of 15.6% ((p < 0.001).Despite the predominance of high-energy mechanism as the primary etiological factor, the incidence of vascular injuries was relatively low, observed in only five patients (2.3%).A similar trend was noted for compartment syndrome, affecting only five patients (2.3%).On average, fractures that did not necessitated staged treatment with external fixation were stabilized using IMN approximately 8.5 ± 5.7 days post-fracture.Importantly, this delay in fixation did not     exhibit any significant association with disturbance in the healing process (p = 0.488).The staged treatment protocol was indicated for 135 patients, comprising 61.9% of our study cohort.Notably, prior use of external fixation demonstrated a strong association with both delayed and non-union outcomes (p < 0.001).This phenomenon can be attributed to the specific indication for external fixation, which is typically reserved for patients with systemic compromise, like polytrauma, or severe soft tissue injuries.Both these factors are known to significantly influence the healing process, potentially delaying, or impeding it.Interestingly, the time to conversion to the IMN, with an average of 6.1 ± 6.1 days, did not exhibit a significant association with disruption in the healing process.
In our research, the utilization of reaming or on-reaming procedures exhibited no statistically significant association with non-union incidence (p = 0.899).The debate surrounding the advantages of reamed nail insertion in the context of fracture healing remains ongoing.A comprehensive systematic review conducted by Clark DR et al. 18 , which included six relevant studies, leans towards endorsing the use of reamed nails.However, it is worth noting that the overall quality of these studies falls within a moderate range.Conversely, Xia L et al. 19 , in their meta-analysis, suggest that reamed nailing may lower the risk of non-union in closed fractures, in a different perspective, Schemitsch EH et al. 20 reported findings that indicate neither reaming nor non-reaming significantly affects reoperation rates.Notably, our series primarily includes open fractures, and this fact seems to align with the argument that reaming may not significantly impact open fracture outcome.The RUST serves as valuable scoring system for assessing progress through radiographic imaging.Our study strongly supports the utility of RUST as a reliable predictor of delayed union at 6-month follow up.Remarkably, for each one-point increase in RUST score, there is in 79% reduction in the likelihood of delayed union (p < 0.001).
To ensure the quality of our results, we deliberately excluded cases involving tibial shaft fractures with significant bone loss.It is selfevident that in absence of a contiguous cortical segment, fracture consolidation is unattainable without a reconstructive procedure.
Our data underscores a observation: when cortical contact falls below 50% in simple type fractures, a significant association with non-union becomes evident (p < 0.001).however, in the case of B type fractures, proximal-to-distal segment contact does not exhibit a statistically significant association (p = 0.999).This discrepancy can likely be attributed to the overriding importance of the size and height of the wedge fragment in influencing the outcome.
In accordance with our expectations, a discernible correlation between postoperative deep infection and non-union has been established (p = 0.002).our observed infection incidence stands at 13.3%, and this is intrinsically linked to the substantial representation of patients afflicted with high-energy trauma and open fractures within our cohort.
Our study aligns with the findings of Ford et al.21 , who reported a 27.9% non-union rate and an 11.5% incidence of deep infection.They identified high-energy trauma, open fractures, and early postoperative complications, including deep.Comorbidities play a diminishing role, whereas open fractures and staged external fixation become more critical.Our study underscores that having less than 50% cortical contact is a significant non-union risk factor, corroborated by Bhandari et al 22 .and Fong et al 3 .The clinical implications is, while these predictors are beyond a surgeon's control, they offer valuable insights for postoperative monitoring and intervention strategies.Although the choice of reaming has minimal impact, achieving a satisfactory reduction with more than 50% cortical contact is crucial, Furthermore, rigorous measures should be taken to prevent deep infection, as they strongly correlate with non-union risk.

CONCLUSION
Our study identifies several key factors associated with heightened risk of non-union following IMN of tibial shaft fracture: high-energy trauma, open fracture, the need for flap procedures, staged external fixation treatment, less than 50% cortical contact, and deep infection.
retrospective study was conducted at urban university-based level one trauma center.Data were collected through a retrospective chart review and the review of existing radiographs from patients with tibial shaft fractures who underwent fixation with IMN, between January 2015 and March 2022.Ethical approval was granted by the Scientific and Ethical Committee (SEC) of the University under the protocol number 24061.Given the retrospective nature of the study, a request was submitted to the SEC to waive the need for the informed consent from the patients, and it was approved.
The inclusion criteria were as follows: age over 18 years, fracture of the tibia shaft, closed or open, treated with intramedullary nailing, follow up radiographs at six months and 12 months, and availability of all necessary data in the patient's charts.The exclusion criteria included pathologic fractures, proximal or distal fractures of the tibia, diaphyseal bone loss, prior injury to the same tibia, and treatments other than IMN.Data were collected on patient's preoperative, intraoperative, and postoperative information.All the relevant data potentially influencing the healing process were collected.These factors were considered to establish their association as risk factor for delayed or non-union.Patient characteristics: age, sex, and race.Trauma energy: high-energy (e.g., car accidents, firearm injuries, fall from height, motorbike accident and vehicle collision) and low energy (e.g., fall from standing height, sports injuries, blunt trauma).Associated injuries: chest and abdominal injuries, neurovascular damage, and fractures in other segments.These injuries were classified according to the Abbreviated Injury Scale (AIS), and subclassified into AIS ≤ 2 and AIS ≥ 39.

Table 2 .
Results related to the treatment.

Table 3 .
Statistical analyzes of healing with 6-month follow up.

Table 4 .
Statistical analyzes of healing with 12 months follow up.

Table 5 .
Multiple regression logistic analyzes of the healing in 6 and 12 months and the risk factors.